The CURE: VA/UCLA Gastroenteric Biology Center is composed of a cohesive group of physicians and basic scientists with strong independent grant- supported research program in gut biology, with special emphasis upon mucosal physiology and disease. CURE first received NIDDK funding in 1974 as a Center to study peptic ulcer disease and became a Digestive Disease Core Center in 1989. The research emphasis of the center is acquisition of new knowledge about cellular processes and physiological control of the gut and translation of this knowledge into development of therapy for patients with gastrointestinal diseases. CURE initially established its reputation for work in clinical peptic ulcer disease, physiological regulation of acid secretion, and parietal cell mechanisms for secreting acid. More recently, demonstration that Helicobacter pylori is an essential factor in pathogenesis of ordinary peptic ulcer disease has brought new aspects of mucosal cell biology into the forefront as the next frontier of research that CURE will follow in its third decade. The interests and activities of Center members have evolved along with science in this area and now include several facets of gastrointestinal regulatory biology including gastrointestinal regulatory peptides, brain-gut interactions, and membrane transport as well as diseases related to these areas. In addition to the parietal cell, other new mucosal cell models have been developed for studies by Center investigators. Functional bowel disease, inflammatory bowel disease, and other disorders of intestinal mucosal function have joined peptic diseases as clinical applications of basic science. The five scientific cores outlined in this proposal provide ready access to technology and to clinical and biological materials that are essential to the programs of Center members. These cores provide custom antibody production, sophisticated peptide chemistry techniques, access to modern cellular imaging to study membrane proteins and their functions, animal models for studying physiology and pathophysiology, and access to a broad range of techniques and patients for clinical studies. An administrative core provides a wide range of administrative support for members and for Center activities including a dynamic enrichment program. The pilot and feasibility program has provided a successful mechanism for aiding development of new research programs by young investigators, and recipients usually have obtained independent funding. The Center provides an optimal environment for cooperation and collaboration among its investigators, who have had a major impact on mucosal biology and on peptic ulcer disease over the past two decades and promise to have an even larger impact upon expanded research areas with continued support from the Center.